Chimerix now 0 for 2 as brincidofovir flunks another PhIII trial

There’s another round of bad news to report for Chimerix. After seeing its stock price crushed at the end of last year on the failure of its first Phase III study for the once-promising antiviral brincidofovir, the Durham, NC-based biotech reports that the treatment flopped in comparison with a historical control group chosen for its late-stage study of adenovirus infections.

CEO Michelle Berrey put the best spin possible on the top-line results, touting the “rapid antiviral effect” tracked in the open-label study, which the company claimed correlated with improved survival rates. But there was no meaningful difference in survival between the historical control group chosen and the drug arm.

Chimerix, which has a habit of trying to explain its way out of bad data, attributed the AdVise study failure on overall survival to a mismatch between the control arm and the drug arm patients. The drug arm was afflicted with a variety of conditions that put them at greater risk of the infections, the biotech noted, leaving investigators with a mismatch.

That won’t do much to restore faith in the drug or the company. Chimerix shares have lost more than 90% of their value from a peak posted last summer. 

Chimerix was forced to reorganize in the wake of its big Phase III failure, dropping two late-stage studies and shedding 20% of its staff as it beat a retreat in the clinic. Its setbacks mark a sharp fall from grace from earlier days, when the company could tout evidence of strong antiviral action. At one point, its refusal to provide the treatment to a young boy struggling for life spurred a viral protest that was the subject of 24/7 cable news coverage. But the company will now have to try to forge a comeback from the shadows. 

Investigators for the failed Phase III cytomegalovirus infection study pinned that setback on a rise in the rate of diarrhea in the drug arm. As diarrhea is a symptom of graft-versus-host disease (GVHD), physicians used corticosteroids more frequently, even though it's also an adverse event associated with the drug, which can be treated by suspending dosing. That use of corticosteroids due to an over-diagnosis for GVHD scuttled the drug's effect, they claim, by increasing the risk of infection.

There were other problems, as well, including no evidence of a reduced rate of non-CMV DNA viruses, such as BK virus. The all-cause death rate was 15.5% for brincidofovir and 10.1% in the placebo arm.

Chimerix was left explaining how it can regroup around an IV formulation in an effort to salvage the company.

“Brincidofovir has demonstrated antiviral activity across a range of viral diseases with limited treatment options,” Berrey said in a statement. “We remain committed to determining the optimal use of brincidofovir in key indications, including the development of intravenous brincidofovir, which is expected to enter clinical studies in the third quarter of 2016. With strong financial resources and patent exclusivity until 2034, we are well-positioned to advance our brincidofovir development program toward potential regulatory decisions.”

Chimerix also reported that it it lost $26 million in Q1, with $314 million in reserves.

- here's the release